PROJECT SUMMARY/ABSTRACT Sport-related concussion is a common and serious injury in the ~7.8 million student-athletes who compete at the high school level each year in the U.S. A successful strategy for reducing the risk of concussion and its associated adverse short- and long-term consequences in this population would advance the mission of enhancing health, reducing illness and disability, and promoting children?s chances to achieve their full potential for healthy and productive lives. Neck strengthening exercise may represent such an intervention. Athletes with smaller, weaker necks are thought to be at increased risk for concussion because their necks are less able to counter the forces acting on their heads during sport-associated collisions, leading to greater resultant net head accelerations. However, our understanding of the mechanism governing the neck?s influence over head acceleration remains incomplete, and the potential for this relationship to be modified by exercise remains unclear. These questions must be answered before neck strengthening exercise programs can be optimized to reduce athletes? risk of concussion. The proposed mechanistic prospective clinical trial will pursue the following specific aims: AIM 1) to determine the effect of manual resistance neck strengthening exercise on neck strength, cervical muscle volume, and net head acceleration under multiple simulated sport- associated impact conditions; AIM 2) to determine the relative influences of neck strength and cervical muscle volume on net head acceleration during simulated sport-associated impacts to the head and body, with and without volitional anticipatory cervical muscle pre-contraction to brace for the impact. The approach to AIM 1 will be to serially reassess the effects of a low or high intensity manual resistance neck strengthening exercise program on key cervical muscle attributes and net head acceleration under each impact condition. Assessments will be performed in 108 high school athletes at baseline and upon completion of 4, 8, and 12 weeks of the exercise intervention, with comparison to a control group participating in a ?shoulders-down? exercise program not specifically targeting the neck. The approach to AIM 2 will be to compare the R2 values of statistical models using baseline data collected with and without anticipatory cervical muscle pre-contraction to predict net head acceleration based on either neck strength, cervical muscle volume, or both. This research is expected to establish dose-response relationships for manual resistance neck strengthening exercise on neck strength, cervical muscle volume, and net head acceleration, as well as define the mechanism by which the neck controls head acceleration during impacts to the head and body with and without anticipatory cervical muscle pre-contraction to brace for the impact. This work will provide important mechanistic insight about how the cervical muscles resist head acceleration that will ultimately lead to improved neck strengthening exercise programs for athletes. In doing so, this work will contribute to the long term objective of reducing concussion- related morbidity through the prescription of neck strengthening exercise.